The present disclosure relates to an implant comprising a matrix material, and a method for manufacturing an implant comprising matrix material. The disclosure further relates to a crimped implant.
A relatively new field of medicine—since the early 1990s—is the field of Regenerative Medicine. Regenerative Medicine is the process of creating living and functional tissues to repair, replace, or restore tissue or organ structure and function lost due to age, disease, damage, or congenital defects. This field of medicine uses new methods including (stem) cell therapy, development of medical devices and tissue engineering.
Over recent years, continuous improvements in our healthcare have resulted in dramatic demographic changes, e.g. an increase in the average age of the population. These demographic changes are causing an increase in the prevalence of diseases associated with aging, such as cardiovascular diseases. Many of these diseases arise from the loss or dysfunction of specific cell types in the human body, leading to permanently damaged tissues and organs.
Cardiovascular diseases are one of the biggest causes of deaths worldwide. One way to treat at least some of these diseases is by tissue engineering. Tissue engineering can be used for the replacement of cardiovascular tissues, such as arteries and heart valves. Currently used cardiovascular substitutes encounter risks due to coagulation, infections, degeneration, and no growth possibilities. Tissue engineering uses patient's own cells and a biodegradable polymer scaffold to make autologous tissue that is able to grow, adapt and repair. To ensure proper cell and tissue growth, the scaffolds must be highly porous and match the mechanical properties of the tissue. Electrospinning is a technique that produces polymer nanofibers using a high voltage electrostatic field. It results in a highly porous material consisting of nanofibers that resembles the extra cellular matrix of the tissue. Tissue engineering can, for example, be used for coronary bypass grafts, heart valve replacements, AV shunts for dialysis patients.
In the field of surgery, minimal invasive surgery is preferred. However tissue engineered constructs can often only be implanted via normal surgical procedures since the constructs cannot be compressed to a size sufficiently small to facilitate minimal invasive surgery. Some artificial heart valves can now be crimped to a diameter of 18 French (6 mm) to allow for implantation via a small peripheral incision (e.g. transfemoral or transjugular). However, many elderly patients in need of a replacement valves also suffer from stenotic and therefore narrowed arteries, which currently excludes them from the much preferred minimal invasive surgery. A reduction of 1 or 2 French in crimpable diameter already means a significant increase in the number of treatable patients.
The technique of tissue engineering consists of constructing substitutes (e.g. biological substitutes) for diseased tissues. Tissue engineering makes use of natural or polymeric scaffolds that provide mechanical support and promote the re-growth of cells lost due to trauma or disease. A scaffold is a temporary structure used to support material (e.g. tissue) during the recovery thereof.
Polymeric scaffolds can be constructed from biocompatible, non-toxic polymers. The choice of polymer and the technique used to make the scaffold effects the mechanical properties exhibited by the scaffold.
In the publication of Bouten et al, Advanced Drug Delivery Reviews, 2011, vol. 63, pp 221-241 synthetic polymers have been demonstrated to be good substrates for valvular and vascular tissue engineering. For cardiac tissue engineering, the most commonly used biodegradable synthetic scaffold materials are polyglycolic acid (PGA), polylactic acid (PLA), polyhydroxybutyrates (PHB), ε-polycaprolactone (PCL) or their co-polymers. No functioning implants were disclosed using the described synthetic scaffold materials.
In the publication by Dankers et al in Nature Materials, 2005, Vol. 4, pp 568-574 solution cast polymer films comprising 2-ureido-4[1H]-pyrmidinone (Upy) polymers were shown to be non-toxic when studied in vivo. However the use of UPy polymers as cardiovascular implant scaffolds was not shown.
In order to obtain a tissue engineered construct, a scaffold can be pre-seeded in vitro with the appropriate cells prior to implantation. In most cases, as the formation and the remodeling of the newly formed tissue proceeds, degradation of the scaffold should slowly and steadily take place, leaving only new healthy tissue behind By “degradation,” it is meant the breakdown of the material into smaller parts, e.g. chemical compounds and/or elements that can be eliminated from the body by means of excretion in urine for example.
A drawback of growing a tissue construct in vitro is that the complete procedure including growing and implanting has to be conducted sterilely making it a costly and laborious procedure. In addition, regulatory guidelines on living tissues are complex, resulting in long and costly processes towards product approval.
Another option is to seed an implant with cells prior to implantation. This method requires the harvesting of cells from the subject to receive the implant, optionally growing the cells in vitro, and seeding the cells in the construct followed by implantation. This method has the same down sides as the previously described method.